This invention relates to a synergistic anticancer combination.
The antimitotic vinca alkaloid vincristine is well known and is currently used clinically in the treatment of neoplasms. The primary effect of this agent is to prevent mitosis by interfering with the function of microtubules, which results in the accumulation of cells in metaphase. The antitumor activity of vincristine against lymphocytic leukemia P388 has been reported by Wheeler et al, Cancer Res., 42, 791 (1982). These experiments were performed by the protocols of the National Cancer Institute, National Institutes of Health as described by Geran et al, J. Cancer Chemother. Rep., 3 (2), 1972. As a clinical agent, vincristine is effective in the treatment of a number of tumors, e.g., leukemias, lymphomas, chloriocarcinoma, Wilm's tumor, neuroblastoma, rhabdomyosarcoma and carcinoma of the testis, and less effective in the treatment of solid tumors, e.g., breast and lung tumors, see Stearn in "The Catharanthus Alkaloids, Botany, Chemistry, Pharmacology and Clinical Uses", Taylor and Farnsworth, eds, Marcel Dekker, Inc., New York, 1973, p. 237.
U.S. Pat. No. 4,450,160 to Temple et al discloses that the compound having the formula: ##STR2## possesses anticancer activity. This compound is one of a series of 1,2-dihydropyrido[3,4-b]pyrazines that have been reported to have antitumor activity against lymphocytic leukemia P388 in mice by Wheeler et al, Cancer Res., 43, 3567 (1983) and Temple et al, J. Med. Chem., 26, 91 (1983). The National Cancer Institute has assigned two National Service Center (NSC) numbers to salts of the compound of Formula I, i.e., NSC 350386 designates the hydrochloride (HCl) salt and NSC 370147 designates the 2-hydroxyethyl sulfonate (HOCH.sub.2 CH.sub.2 SO.sub.3 H) salt.
Wheeler et al in Cancer Research, 43, pages 3567-3575, Aug., 1983, discloses the synergistic cytotoxicity of a combination of vincristine and a compound having the formula: ##STR3##